Although estrogens have been thought to affect the prostate primarily via the hypothalamic-pituitary-testis axis, critical direct effects of estrogens on the prostate have recently been demonstrated. The significance of such direct action both in the pathogenesis of prostatic carcinoma and in the development of new agents, e.g., Estracyt, for the treatment of this disease suggests further investigation. Since cytoplasmic receptors are critical to the action of steriod hormones, it is important to note that we have recently demonstrated the presence of estrogen receptors in the baboon prostate. Our present objective is to extend these observations, to study the effects of new chemotherapeutic agents (steriod-mustards as well as other antineoplastic drugs) on prostatic estrogen binding in both animal and human prostatic tissue. The potential clinical application of this investigation is the elucidation of the mechanism of action and the testing of various compounds effective in the treatment of prostatic carcinoma. Such investigations will require the development of methods to isolate cytosol-receptor steroid complexes. Such complexes, moreover, must be free of plasma binding protein. Our methods will include the use of both human and animal (baboon and rat) tissue. In this regard, it is important to note that the baboon, rat and human prostates all are separable into lobes which are at least functionally and biochemically different. The propensity of human prostatic carcinoma to originate in the peripheral or so-called posterior lobe will make such comparisons important. To isolate, characterize and further study estrogen receptors, we will use sucrose density gradient centrifugation, Sephadex-column chromatography and agar-gel electrophoresis and fractionation.